Effects of Medication Period and Gastrin Levels on Endoscopic Gastric Mucosal Changes in Long-Term Proton Pump Inhibitor Users

<b>Background/Objectives</b>: Proton pump inhibitor (PPI) use has increased worldwide, including in continuous and longer-term users. Recent reports highlight PPI-related endoscopic gastric mucosal changes, including fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cracked and cobblestone-like mucosa (CCLM), and black spots. PPI use elevates gastrin levels because of acid inhibition, and hypergastrinemia might be relevant to these findings. In this cross-sectional study, we retrospectively examined gastric mucosal changes in long-term PPI users, focusing on medication period and gastrin levels. <b>Methods</b>: We enrolled 57 patients who received a PPI (>1 year) at two clinics between January 2021 and March 2022. Participants were classified according to medication period: 1 < 5, 5-10, and ≥10 years. Gastrin levels were categorized as low, middle, and high (<250, 250-500, and ≥500 pg/mL, respectively). Odds ratios (OR) were estimated to assess the risk of endoscopic findings. <b>Results</b>: Of the 57 patients, 6 (10.5%), 25 (43.9%), and 26 (45.6%) were PPI users of 1 < 5, 5-10, and ≥10 years, respectively. There were no significant differences in the incidence of endoscopic findings among the medication periods. Low, middle, and high gastrin groups included 21 (36.8%), 21 (36.8%), and 15 (26.3%) patients, respectively. CCLM incidence was significantly elevated in higher gastrin level groups: middle (OR, 6.60; 95% confidence interval [CI], 1.46-29.75; <i>p</i> = 0.014) and high (OR, 9.00; 95% CI, 1.79-45.23; <i>p</i> = 0.0008) (p-trend = 0.0171). No significant differences were observed for other findings. <b>Conclusions</b>: No elevated risk of PPI-related gastric epithelial changes in long-term PPI users was observed time-dependently. Notably, higher gastrin levels were positively associated with CCLM development, irrespective of the medication period.